Non-digestible sugar-coated products and process

ABSTRACT

A method and composition are provided for coating a component to achieve colon-targeted delivery. A component is coated with a fructose-based non-digestible carbohydrate such as a inulin, fructo-oligosaccharide or neosugar. The coated component is orally administered to a monogastric animal. The non-digestible coating causes the composition to pass through the stomach and small intestine without being degraded, and delivers the component to the colon where the coating is digested by microbial fermentation and the component is released.

[0001] This application is being filed as a PCT International PatentApplication in the name of BioMatrix, Inc., a U.S. national corporationand resident, (Applicant for all countries except US) and Guy W. Miller,a U.S. resident and citizen (Applicant for US only), on 17 Apr. 2002,designating all countries and claiming priority to U.S. ProvisionalApplication Serial No. 60/284,389 filed Apr. 17, 2001.

BACKGROUND

[0002] 1. Field of the Invention

[0003] This invention is directed to methods and compositions forcolon-targeted delivery of components.

[0004] 2. Description of the Prior Art

[0005] Fructan is a non-structural carbohydrate and is a polymer offructose. Fructans have a general structure of a glucose linked tomultiple fructose units. There are several types of fructans present innature, and they can broadly be divided into 3 groups: inulins,fructo-oligosaccharides (FOS), and neosugars.

[0006] Inulin is a polydisperse fructan extracted from plants, includingchicory root, asparagus shoot, banana, dandelion, garlic, globeartichoke, Jerusalem artichoke, leek, onion, rye, salsify, and wheat,that has not been digested enzymatically by inulinase. The chemicalstructure of inulin is shown in FIG. 1. GF_(n) is a glucose endingfructan chain, and n represents chain length. Inulin has a degree ofpolymerization (DP) in the approximate range of 2 to 60 units of β(2-1)fructose with a glucosyl terminus. The average DP is greater than 10units.

[0007] Fructo-oligosaccharide (FOS) is partially hydrolyzed inulin witha DP in the approximate range of 2 to 20 units of β(2-1) fructose witheither a glucosyl or a fructosyl terminus. The average DP is less than10 units. Chemical structures of glucose ending fructan chains (GF_(n))and fructose ending chains (F_(n)) are shown in FIGS. 2A and 2B. Inulinis hydrolyzed with inulinase, for example, to producefructo-oligosaccharides.

[0008] Neosugars are fructo-oligosaccharides that can be prepared, forexample, by an enzymatic reaction using sucrose and the enzymefructosyltransferase from an organism such as Aspergillus niger. Thechemical structure of neosugar is shown in FIG. 3. Neosugars have DP inthe approximate range of 2 to 4 units of β(2-1) fructose with a glucosylterminus. The average DP is about 2 to 3 units. Collectively, inulin,FOS, and neosguars are referred to herein as fructans.

[0009] Fructans are currently used as an animal feed supplement, mixedwith the animal feed. Fructans are found in the feed of monogastricanimals, including poultry, turkey, swine, dog, cat, horse, and bovinecalf diets. (Bovine calves begin their development as monogastricmammals). Fructans are also added to food and drink for humanconsumption. As an oral supplement, fructans have been shown to improveweight gain, reduce fecal odor, reduce colon cancer, lower bloodtriglycerides, increase mineral uptake, and promote a healthygastrointestinal system.

[0010] Fructans are essentially “non-digestible” by monogastrics; theyare not digested in the stomach or small intestines. Consequently, thefructan-coated components of the instant invention are not digested inthe stomach of monogastric mammals and pass directly to the colon wherethe fructan is fermented by organisms residing in the colon. Asfructan-fermenting bacteria grow, there is a concomitant decrease in theconcentrations of putrefactive bacteria such as Escherichia coli,Clostridium perfringens and Salmonella, which are widely known toproduce malodorous aromatic metabolites. Bacteria that utilize fructansas a source of energy include beneficial bacteria in the genus ofBifidobacterium and Lactobacillus. Non-digestible ingredients, such asfructans, that beneficially affect the host by selectively stimulatingthe growth and/or activity of bacteria in the colon that can improvehost health and known as “prebiotics”.

[0011] Wang et al. (Journal of Applied Bacteriology, 75:373-380, 1993)looked at mixed populations of colonic bacteria in a batch culture grownon inulin, fructo-oligosaccharide, polydextrose and starch. The type ofcarbohydrate used in each batch culture had no effect on total aerobic,anaerobic or Bacteriodes counts. Bifidobacteria counts were 5 to 13times higher with batch cultures grown on fructo-oligosaccharide andinulin then polydextrose and starch. The coliform counts were 8 to 630times lower with batch cultures grown on inulin andfructo-oligosaccharide than polydextrose and starch. Lactobacilluscounts were 316-1,000 times lower in batch cultures when inulin was usedas a substrate than fructo-oligosaccharide, starch and polydextrose.

[0012] In order for inulin and fructo-oligosaccharides to affect themicrobial population in the colon, they must first pass through thestomach and small intestine. Samples taken from the ileum of humansreceiving diets containing inulin or fructo-oligosaccharides have beenshown to exhibit an 89% and 88% recovery respectfully (Ellegard et al.,European Journal of Clinical Nutrition, 51:1-5, 1997). Similarly, humansreceiving Neosugar in their diet have been shown to exhibit an 89%recovery in ileal samples taken (Molis et al., American Journal ofClinical Nutrition, 64:324-328, 1996). The fraction of fructan that isnot recovered is digested in the gastrointestinal tract and thenabsorbed as glucose or fructose. The digestion may have occurred in theileum via bacterial fermentation or by acid digestion in the stomach(Simon et al., Gastroenterology, 86:174-193, 1984). In vitro studieshave shown that fructans and inulin are hydrolyzed at a low rate and avery low pH (Nilsson et al., Journal of Nutrition, 86:1482-1486, 1988).

[0013] Once the fructans reach the colon, they are fermented completelyby the microbial flora. (Jenkins et al., Journal of Nutrition,129:1431S-1433S, 1999). With fermentation of the fructans in the colon,changes occur to the microbial flora. Most notably, the Bifidobacteriasp., has been shown to increase 5 to 63 fold (Djouzi et al., BritishJournal of Nutrition, 78:313-324, 1997). A review by Loo et al. (BritishJournal of Nutrition, 81:121-132, 1999) of ten trials studying theincrease in Bifidobacteria sp. in the colon of humans receiving inulinor fructo-oligosaccharide in their diets showed a statisticallysignificant increase in Bifidobacteria sp. The average for the ninetrials was an 11.8-fold increase in Bifidobacteria sp. with a high of a22-fold increase. Other changes that were observed in colonicpopulations of humans receiving inulin and fructo-oligosaccharideinclude the significant decrease in Bacteriodes sp. and/or Clostridiasp. (Gibson et al., Journal of Nutrition, 125:1401-1412, 1995; Kleessenet al., American Journal of Clinical Nutrition, 65:1397-1402, 1997).

[0014] The increase of Bifidobacteria has been shown to be correlated toa dose response to fructan addition to the diet. Studies have shown thathumans subjects exhibit no increase in Bifidobacteria sp. until theirdiet contains 10 grams of Neosugar per day (Bouhnik et al., Journal ofNutrition, 129:113-116, 1999). A review by Roberfroid et al. (Journal ofNutrition, 128:11-19,1998) combined data for inulin,fructo-oligosaccharide and Neosugar and concluded that log increases incounts do not correlate to daily doses administered. One variableconsidered to correlate with increases was the initial number ofBifidobacteria in the feces. It appeared that the lower the initialnumber, the greater the increase whatever the dose, within the range of4 to 20 or more grams per day. Consuming a few grams of any of thesefructans daily could be sufficient to cause a significant increase incolonic Bifidobacteria.

SUMMARY OF THE INVENTION

[0015] According to one embodiment of the present invention, a methodand composition are disclosed for coating a component to achievecolon-directed delivery. The invention includes coating a component witha non-digestible composition, such as a fructan, to produce a feedsupplement. The coated component, a non-digestible coated composition,is administered to a monogastric animal, where the non-digestible coatedcomposition passes through the stomach and small intestine without beingdegraded, and is delivered to the colon where the coating is digestedand the component is released.

[0016] According to a preferred embodiment of the present invention, theindigestible coating is fructan.

BRIEF DESCRIPTION OF THE DRAWINGS

[0017]FIG. 1 shows the chemical structure of inulin.

[0018]FIGS. 2A and 2B show chemical structures offructo-oligosaccharides.

[0019]FIG. 3 shows the chemical structure of neosugar.

DETAILED DESCRIPTION OF THE INVENTION

[0020] The present invention is directed to a method and composition forcoating a component for delivery targeted to the colon of an animal. Itis often desirable to deliver components, such as drugs, vitamins,minerals, metabolites, beneficial bacteria, and other molecules, to thecolon of an animal without subjecting the component to the acids anddigestive enzymes of the stomach and small intestine.

[0021] Administration by conventional means, including oral,intravenous, percutaneous, or other known delivery methods, generallyresults in reduced bioavailability of the component. Degradation oralteration of the component by digestive enzymes and/or low pH may occurin the stomach and small intestine when conventional oral preparationsare used, reducing or inactivating the therapeutic activity of thecomponent.

[0022] Intravenous and percutaneous administration generally requires alarge dosage, sufficient to ensure that the desired level of thecomponent reaches the colon. Such routes of administration are generallynot suitable for components such as beneficial bacteria and manyvitamins, minerals and metabolites.

[0023] Drugs can be targeted to the colon by coating the drugformulations with polymeric coatings, such as acrylic acid derivativesor cellulose derivatives, that can withstand both low and slightly basicpH values for several hours. A disadvantage of this targeting method isthe uncertainty of location and environment in which the polymericcoating will be degraded. The delay in coating degradation is based onthe amount of time spent in a particular pH environment. If the coateddrug is delayed in the upper gastrointestinal tract, such as formechanical reasons, the drug may be released in a non-target location,such as the small intestine.

[0024] The present invention provides a safe and effective method andcomposition for targeting components specifically to the colon based onthe presence or absence of bacteria that degrade a prebiotic, such asfructan. The components to be administered are coated with a prebioticthat is not digested in the stomach or small intestine, but that isdegraded by bacteria present in the colon, especially of monogastricanimals.

[0025] As used herein, “prebiotic” is intended to mean a non-digestiblefood ingredient that beneficially affects the host by selectivelystimulating the growth and/or activity of one or a limited number ofbacteria in the colon, that can improve host health. Oligosaccharidessuch as inulin, fructo-oligosaccharide and neosugar, which cannot bedigested except through bacterial activity, are considered prebiotics.Many other carbohydrates can be considered prebiotics, for example,those listed in

[0026] Table 1. Other ingredients that reach the colon undigested andcan be considered prebiotics include peptides, proteins, and lipids.Criteria for classifying a substance as a prebiotic may include:

[0027] 1. Not hydrolyzed or absorbed in the upper part of thegastro-intestinal tract.

[0028] 2. Selectively fermented by potentially beneficial bacteria inthe colon.

[0029] 3. Alters the composition of the colonic microbial flora towardsa healthier composition.

[0030] 4. Preferably, induces effects that are beneficial to the hosthealth. TABLE 1 Candidate Prebiotic Carbohydrates OligosaccharideChemical Composition Fructo-oligosaccharide β(2-1) fructan with degreesof polymerization ranging from 2-20 units and has an average degrees ofpolymerization of 2 to 10 Inulin β(2-1) fructan with degrees ofpolymerization ranging from 2-60 units and has an average degrees ofpolymerization greater than 10 Neosugar β(2-1) fructan with degrees ofpolymerization ranging from 2-4 units and has an average degrees ofpolymerization from about 2 to about 3 Polydextrins Complex mixture ofglucose-containing Oligosaccharide Transgalactosylated Mainly6′galactosyllactose, DP of oligosaccharide oligosaccharides fraction 2-5(primarily DP 3); 55% pure Galacto- Oligogalactose (85%), small amountsof glucose, oligosaccharides galactose, and lactose Soyaoligosaccharides Stachyose (fructose, galactose, galactose, glucose) andraffinose (fructose, galactose, glucose), DP 3-4 Xylo-oligosaccharidesB(1-4) linked xylose; 70% pure, DP of oligosaccharide fraction is 2-4Isomalto- Mixture of α(1-6) linked glucose oligomers oligosaccharides(isomaltose, panose, isomaltotriose) Lactulose Galactose andfructose-containing disaccharide

[0031] Many bacteria can utilize fructans for growth. These includelactic acid bacteria, such as Lactobacillus sp. and Bifidobacterium sp.,which are considered probiotics. Many bacteria, such as, Escherichiacoli and Salmonella sp. cannot utilize fructans for growth.

[0032] As used herein, “non-digestible” is intended to mean that asubstance taken orally is substantially resistant to chemical andenzymatic degradation in the stomach and small intestine, but issusceptible to degradation in the colon.

[0033] As used herein, “monogastric” is intended to encompass any animalhaving one stomach. Examples of monogastric animals include, but are notlimited to, horses, emu, ostrich, dog, cat, swine, bear, turkey,chickens, ducks, quail, pheasants, reptiles, and humans. Pre-ruminantanimals such as young cattle, buffalo, bison, and elk are alsoencompassed by the term monogastric as these animals are bornmonogastric and then develop into true ruminants as adults.

[0034] Additionally, the compositions and methods of the presentinvention are suitable for any animal that breaks down fructose-basedoligosaccharide selectively in a specific part of the gastrointestinaltract. Breakdown of a fructose-based oligosaccharide generally requiresthe presence of bacteria capable of fermenting the oligosaccharides,such as those from the genus Bifidobacterium and Lactobacillus. Thecompositions of the invention can be selectively delivered to the colonby administration of the coated composition to any animal havingfructan-fermenting bacteria present in at least part of their digestivetract. For those animals having insufficient Fructan-fermenting bacteriain their digestive tract, Fructan digesting bacteria can be optionallyadded along with the diet.

[0035] As used herein, “component” is intended to encompass anycompound, molecule composition, or organism that is to be coated anddelivered to the colon in the method of the invention. Examples include,but are not limited to, minerals, vitamins, drugs, bacteria, yeast,immune stimulators, nutrients, nutraceuticals, electrolytes, chelatedminerals, molds, enzymes, energy-providing compounds, antibodies, andacids.

[0036] Minerals for colon-targeted delivery include, but are not limitedto, calcium, chromium, cobalt, copper, iodine, iron, magnesium,manganese, organic trace minerals, phosphorus, potassium, selenium,sodium, sulfur, zinc, and the like. Vitamins include, but are notlimited to, vitamins A, B12, C, D, E, K, betaine, biotin, choline, folicacid, inositol, niacin, pantothenic acid, pyridoxine, riboflavin,thiamine, etc. Drugs include, but are not limited to, antibiotics,anti-viral agents, anti-mold agents, bloat preventatives, coccidiostats,growth enhancers, vaccines, wormers, chemotherapy agents, anti-tumoragents, insulin, etc. Examples of suitable drugs include Aureomycin 90,Aureomix 500, BMD 60, ChloMax-SP 500, Denagard 10, Lincomix 50, Mecadox10, Neo-Terramycin 50/50, Pulmotil 90, Tylan 100, and 3-Nitro20.

[0037] Bacteria to be introduced into the colon include any beneficialbacteria, including, but not limited to, Bacillus coagulans, Bacilluslentus, Bacillus licheniform is, Bacillus pumilus, Bacillus subtilis,Bacteroides amylophilus, Bacteroides capillosus, Bacteroides ruminocola,Bacteroides suis, Bifidobacterium adolescentis, Bifidobacteriumanimalis, Bifidobacterium bifidum, Bifidobacterium infantis,Bifidobacterium longum, Bifidobacterium thermophilum, Entercoccuscremoris, Entercoccus diacetilactis, Entercoccusfaecium, Entercoccusintermedius, Entercoccus lactis, Entercoccus thermophilus, Lactobacillusacidophilus, Lactobacillus brevis, Lactobacillus bulgaricus,Lactobacillus casei, Lactobacillus cellobiosus, Lactobacillus curvatus,Lactobacillus delbruekii, Lactobacillus fermentum, Lactobacillushelveticus, Lactobacillus lactis, Lactobacillus plantarum, Lactobacillusreuteri, Leuconostoc mesenteroides, Pediococcus acidilactici,Pediococcus cerevisiae, Pediococcus pentosaceus, Pripionibacteriumfreudenreichii, Propionibacterium sherimanii, Streptococcus cremoris,Streptococcus diacetilactis, Streptococcus faecium, Streptococcusintermedius, Streptococcus lactis, and Streptococcus thermophilus.

[0038] Yeast include, but are not limited to, Saccharomyces sp. andCandida sp., more specifically Saccharomyces cerevisiae and Candidautilis. Immune stimulators include, but not limited to,mannose-oligosaccharide and beta-glucan. Nutrients include, but are notlimited to, amino acids such as arginine, glycine, lysine, methionine,taurine, threonine and tryptophan, peptides such as insulin, proteins,carbohydrates, amino acids, bone meal, grains, egg, fats and oils,feather meal, fish meal, plant and animal byproducts, plasma, poultrybyproducts, whey, and the like.

[0039] Nutraceuticals include, but are not limited to, spices, essentialoils, soy products and natural extractives such as alfalfa, angelica,anise, basil, bay leaf, calendula, camomile, caraway, cardamom, carrot,cayenne pepper, chicory, celery seed, chives, cinnamon, cloves,coriander, cumin, dandelion, dill, fennel, fenugreek, garlic,glycyrrhiza, habanero pepper, horehound, horsemint, horseradish, hyssop,gentian, ginger, ginseng, juniper, kava, lemon balm, lemon grass,licorice, marjoram, melissa, mustard, netmeg, nettle, onion, oregano,parsley, pepper, peppermint, raspberry, rosemary, rue, savory,spearmint, tarragon, thyme, and vanilla.

[0040] Nutraceuticals also include, but are not limited to, herbs suchas Boneset or Feverwort (Eupatorium perfoliatum), Burdock (Arctiumlappa), Coltsfoot (Tussilago farfara), Comfrey (Symphytum officinale),Devil's Claw Root (Harpagophytum procumbens), Ginkgo (Ginkgo biloba),Golden Rod (Solidago virgaurea), pot Marigold (Calencula officinalis),Meadowsweet (Filipendula ulmaria), Monk's Pepper or Chasteberry (Vitexagnus-castus), Nettle (Urtica dioicea), Red Poppy Seed (Papaver rhoeas),Raspberry leaves (Rubidus idaeus), Valerian root (Valerianaofficinalis), Vervain (Verbena ojficinalis), and Yellow Dock (Rumexcrispus).

[0041] Electrolytes include, but are not limited to, potassium,magnesium, and calcium. Chelated minerals include, but are not limitedto, copper, zinc, iron, manganese, chromium and magnesium bound to aprotein or carbohydrate source. Examples include, but are not limitedto, Alfamin® from RK Marketing Enterprises, Inc. (Waconia, Minn.) andSQM from Quali Tech Inc. (Chaska, Minn.). Other companies that producechelated minerals include Albion Laboratories, Inc. (Clearfield, Utah),Zinpro Corporation (Eden Prairie, Minn.) and Chelated Minerals (Ogden,Utah). Molds include, but are not limited to, Aspergillus niger andAspergillus oryzae. Enzymes include, but are not limited to, cellulase,hemicellulase, anylase, phytase, and ligninase. Energy-providingcompounds include, but are not limited to, sugars such as glucose,sucrose, fructose, propylene glycol and glucose precursors.

[0042] Antibodies include, but are not limited to, those reactive withspecific bacteria and viruses and those reactive with broad classes ofbacteria and viruses. Acids include, but are not limited to, citricacid, lactic acid, and acetic acid. Additionally, other components,including emulsifiers and surfactants, acidifiers, buffers, dietaryfiber, flavoring agents, attractants, flow and anti-caking agents, grit,kelp meal, algae, molasses, pigments, preservatives, antioxidants moldinhibitors, sweeteners, urea, yucca products, and other components, canbe coated by the method of the invention for colon-targeted delivery.

[0043] In another embodiment of the present invention, the fructancoating is used to mask or cover-up an otherwise unpalatable component.Examples of unpalatable components include, but are not limited to,ammonium chloride, calcium sulphate, magnesium chloride, propyleneglycol, drugs, vitamins, and other ingestible compositions. In thisinstance, the Fructan coating is provided to provide a more organolepticcomposition.

[0044] In a further embodiment of the present invention, the fructancoating is used to prevent or minimize the release of components thatmay be disruptive or harmful to the stomach or small intestine. Forexample, chemotherapy and anti-tumor agents directed to a tumor in thecolon may cause undesirable effects if released in the uppergastrointestinal tract.

[0045] The coating of the present invention can also be used to improvethe flowing characteristics of a component. This is especiallybeneficial for components that are sticky, powdery, viscous, etc. intheir uncoated state.

[0046] The coating can be applied by conventional methods, includingfreeze-drying, spray-coating, mixing, agglomeration, and combining arapid centrifugal application of liquid and powder to create a thin filmpolymer coating using a rotary disc type liquid/powder applicator.

[0047] In one embodiment, the component to be delivered to the colon iscoated with fructan using a rotary driven disc system. The component canbe in the form of pellets, tablets, pieces, nuggets, crumbles, and thelike, that may be of any size, and may be regular or irregular in shape.The pellets may be, for example, in the approximate size range of 10microns to 100 microns in diameter. In this system, the pellets aredropped on the disc as it rotates. This rotation carries the pellet outto the chamber wall by centrifugal force. As the pellet is turned bymixing blades mounted on the chamber walls, powdered fructan and liquidor a mixture of the fructan and liquid are introduced into the chamber.Liquid, such as water or a mixture of water and fructan, is atomized bythe high-speed disc into ultra-fine particles that are applied to thepellets. The process results in a thin film coating of the carbohydrateon the component pellets.

[0048] Probiotic bacteria such as Lactobacillus sp. and Bifidobacteriasp. are known for their ability to ferment fructans while Escherichiacoli and Salmonella sp. cannot. In the colon, this positive change inthe microbial population leads to a healthier intestinal tract whichimproves immune response, weight gain, feed efficiency, nitrogenretention, mineral absorption and increased short-chain fatty acidsproduction. Other positive benefits include reduced colonization of theintestinal tract by enteric bacteria, reduced diarrhea, reduced stomachupsets, firmer feces and an increased energy source for hyperglycemicanimals such as dogs, cats and veal calves.

[0049] The chain length of the fructan is fermented differently bydifferent species of probiotic bacteria. The longer DP fructan isfermented half as fast as fructans with shorter DP. A coatingcomposition having a longer chain length such as inulin may be wellsuited for a positive prebiotic effect throughout the colon.Fructo-oligosaccharide and Neosugar are considered a shorter DPfructans, and may be well suited for quick delivery to the colon.Combinations can produce a variety of degradation effects, as desired.

[0050] Pure cultures of different species of Bifidobacteria have beenshown to have different growth rates when grown onfructo-oligosaccharide. In other studies mixed cultures ofBifidobacterium infantis, Escherichia coli and Clostridium perfringensgrown on fructo-oligosaccharide have shown an inhibitory effect towardsEscherichia coli and Clostridium perfringens.

[0051] The favorable effects of soluble fiber for diabetes mellitus mayalso be favorable for veal calves. Veal calves in late fatting periodsoften develop hyperglycemia, glucosuria, and insulin resistance withhigh lactose intakes. Kaufhold et al. (Journal of Veterinary Medicine47(1):17-29,2000) has reported higher weight gains in veal calvesreceiving fructo-oligosaccharide. The study also showed calves receivingfructo-oligosaccharide had a lower post-prandially increase in glucoseand higher insulin concentrations. They concluded thatfructo-oligosaccharide has similar endocrine traits in veal calves as inhumans with diabetes mellitus. Mul (“Application of Oligosaccharides inAnimal Feeds”, in Proceedings: International Symposium on Non DigestibleOligosaccharides: Health Food for the Colon?, Wagneningen, Netherlands,1997) reported on field trials by Trouw Nutrition from 1990-1992 withveal calves. The majority of the field trials showed improved weightgain (0.8-2.4 kg), improved feed efficiency (3-14%), reduction indiarrhea incidence, and on average firmer feces. In one reported trial,higher weight gains were observed when a probiotic was used incombination with fructo-oligosaccharide.

[0052] The amount of the component to be administered will varydepending on the desired effect to be achieved, and depending on thespecies, age, sex, physical condition, disease state, diseaseprogression, etc., of the subject receiving the component. When thecomponent is a drug, the amount administered will also depend on thedrug's efficacy. In general, it would be expected that the dosage ofdrug required to achieve a particular result, and delivered directly tothe colon, will be less than the dosage required for intravenous,conventional oral or other systemic delivery.

EXAMPLE 1 Coated Polypropylene Glycol in Dairy Cows

[0053] In this coating trial, the propylene glycol product (Glycopulp)was coated with FOS (bioSecure™) as the coating agent. The use ofpropylene glycol as a glucogenic supplement for dairy cows during thetransition phase from the middle of the dry period through the first 21days of lactation is known. However, the addition of propylene glycol tothe total mixed ration (TMR) is known to decrease feed intake.

[0054] The propylene glycol product (Glycopulp) was masked with a feedflavor, and coated with FOS as the coating agent. The drying agent waschicory pulp and the flavoring agent was Milk Buds™ F.S.

[0055] Glycopulp is a blend of chicory pulp (1 mm screen) and feed gradepropylene glycol in a ratio of 55:45 (W/W). The Glycopulp was suppliedby Socode S.C. (Warcoing, Belgium). Chicory pulp (1 mm screen) was usedas a drying agent during the coating process. The FOS used as thecoating agent was suspended in water prior to coating.

[0056] The flavoring agent, Milk Buds™ F.S. (Lot No. 8176) was suppliedby QualiTech (Chaska Minnesota, Product Code 2741). The flavoring agentcan be added to feed, for example, at a rate of about 0.25-4 ounces perton of finished feed. In this trial, a rate of approximately 2 ouncesper ton of finished feed was used. The flavoring agent was suspended inwater with the FOS prior to coating.

[0057] Coating Process

[0058] Engineered Technology Systems, Inc. (ETS, Gilroy, Calif.) offerscoating equipment to the agricultural seed market sector, manufacturedfood industries and pharmaceutical industry. The approach to the ETSline of coating systems is the rapid application of liquid and powdermaterials to create a thin film polymer coating, build-up coating orspherical pellet. The system “coats” products by centrifugal force asthe product travels rapidly around the stator (bowl) via the movement ofa rotor. The rotor is the bottom end of the equipment that moves theproduct by centrifugal force. The atomizer sits slightly above therotor. The atomizer is a small spinning disk through which liquids arepumped via peristaltic pumps at precise rates. When liquids hit theatomizer the liquids are atomized into small particles that areprojected onto the materials being moved around the stator. Powders canbe injected into the coating equipment at any time during the process toallow a “build-up” process to form around a nucleolus (nucleolus beingthe product coated). The equipment achieves all of these functions bycomputerized controls that monitor and provide operator feedback. Theentire coating process is a controlled semi-continuous system where aknown amount of material is coated at one time. The production rate ofeach coating run takes only seconds to achieve the desired product.

[0059] Trial 1

[0060] The proportions of components used for this trial are found inthe table below. Three hundred twenty grams of polyethylene glycol(Glycopulp) was placed into the drum of the ETS R-12 rotary coater. Themoving rotor was turned on and it was determined that the sampleadequately flowed in the equipment to be coated. Thirty-two millilitersof Stock Solution A (FOS and water) was applied to the rotatingGlycopulp. After applying Stock Solution A, 17.5 grams of chicory pulp(1 mm screen size) was applied as a drying agent. Drying can also beachieved by low temperature air. Trial One, No Flavor Added Item AmountStock Solution A: BioSecure FOS 11 grams Water 2 liters Glycopulp 320grams Chicory Pulp 17.6 grams

[0061] Trial 2

[0062] The proportions of components used for this trial are found inthe table below. Three hundred twenty grams of Glycopulp was placed intothe drum of the ETS R-12 rotary coater. The moving rotor was turned onand it was determined that the sample adequately flowed in the equipmentto be coated. Thirty-two milliliters of Stock Solution B (FOS, flavoragent, and water) was applied to the rotating Glycopulp. After applyingStock Solution B, 17.5 grams of chicory pulp (1 mm screen size) wasapplied as a drying agent. Drying can also be achieved by lowtemperature air. Trial Two, Flavor Added Item Amount Stock Solution B:BioSecure FOS 11 grams Milk Buds 1.2 mls Water 2 liters Glycopulp 320grams Chicory Pulp 17.6 grams

[0063] The source of fructo-oligosaccharide (FOS) in bioSecure™ FOS isderived from chicory roots. Chicory roots are a natural source ofinulin; a carbohydrate made up of fructose polymers (fructan). Thefructan cannot be metabolized by monogastrics, which lack the enzymeinulinase. Consequently, fructan passes on to the lower intestine whereit is fermented by lactic acid producing bacteria such asBifidobacterium. Gram negative bacteria such as Escherichia coli areunable to ferment or grow on fructan; thereby a natural selection willtake place promoting beneficial bacteria in the lower intestine.

[0064] The following analysis of bioSecure™ FOS is exemplary only. Asinulin and fructo-oligosaccharide are natural products, their exactcomposition will vary from crop to crop and from year to year.Additionally, the enzymatic breakdown of inulin with inulinase can vary.Neosugars are produced by an enzymatic reaction and can also vary in theend result. Analysis of bioSecure ™ FOS % Item Dry Matter 95Carbohydrate Content 99.9 Ash 0.1 Carbohydrates Free Sugars 8.2 Glucose0.7 Fructose 2.9 Sucrose 4.6 DP 1-10 41.1 DP 11-20 30.0 DP 21-30 17.5 DP31-40 7.7 DP 41-50 2.6 DP 51-60 1 DP 3-20 61.8 Average DP_(n) 6.6

[0065] Specifications of bioSecure ™ FOS Analysis Specification ResultsDry Matter (%) 95% Minimum 97.1% Ash (% of DM) 0.5% Maximum 0.1%Carbohydrate content 99.5% Minimum 99.9% (% of DM) Free Sugars (% of DM)10% Maximum 9.1% Fiber (% of DM) 90% Minimum 90.8% Total Plate Count10,000 cfu/gm Maximum 110 cfu/gm Yeasts 20 cfu/gm Maximum <10 cfu/gmMolds 20 cfu/gm Maximum <10 cfu/gm Coliforms 0 cfu/gm 0 cfu/gm

[0066] Having described the invention, alternatives and embodiments mayoccur to one of skill in the art. It is intended that such modificationsand equivalents shall be included within the scope of the followingclaims.

I claim:
 1. A method of delivering a component to the colon of an animalcomprising: coating the component with a fructose-based non-digestiblecarbohydrate; and orally administering the coated component to theanimal.
 2. The method of claim 1 wherein the fructose-basednon-digestible carbohydrate is fructan.
 3. The method of claim 2 whereinthe fructan has an average degree of polymerization in the approximaterange of 2 to
 60. 4. The method of claim 3 wherein the fructan has anaverage degree of polymerization in the approximate range of 2 to
 20. 5.The method of claim 4 wherein the fructan has an average degree ofpolymerization in the approximate range of 2 to
 10. 6. The method ofclaim 1 wherein the fructose-based non-digestible carbohydrate isfructo-oligosaccharide.
 7. The method of claim 1 wherein thefructose-based non-digestible carbohydrate is neosugar.
 8. The method ofclaim 1 wherein the component is one or more of a mineral, vitamin,drug, bacteria, yeast, immune stimulator, nutrient, nutraceutical,electrolyte, chelated mineral, mold, enzyme, energy-providing compound,antibody, or acid.
 9. The method of claim 8 wherein the component isbacteria from the genus Lactobacillus or Bifidobacterium.
 10. The methodof claim 8 wherein the component is a nutraceutical.
 11. The method ofclaim 8 wherein the component is an enzyme.
 12. The method of claim 8wherein the component is an immune stimulator.
 13. The method of claim 8wherein the component is a drug.
 14. The method of claim 1 wherein thefructose-based non-digestible carbohydrate is utilized as an energysource by Bifidobacterium species, but not by Salmonella species. 15.The method of claim 1 wherein the fructose-based non-digestiblecarbohydrate is utilized as an energy source by Lactobacillus species,but not by Escherichia coli.
 16. The method of claim 1 wherein thecoating step comprises applying powdered fructose-based non-digestiblecarbohydrate with a liquid to form a thin film coating on the component.17. The method of claim 16 further comprising repeating the step ofapplying the powdered fructose-based non-digestible carbohydrate andliquid to achieve a multi-layered coating.
 18. The method of claim 1wherein the coating step comprises combining the fructose-basednon-digestible carbohydrate with a liquid to form a mixture andatomizing and spraying the mixture on the component to form a thin filmcoating on the component.
 19. The method of claim 18 further comprisingrepeating the step of applying the fructose-based non-digestiblecarbohydrate and liquid mixture to achieve a multi-layered coating. 20.The method of claim 1 comprising coating the component withfructose-based non-digestible carbohydrate and one or more flavoringagent.
 21. The method of claim 1 wherein the component is a bacteria.22. The method of claim 21 wherein the bacteria is from the genusLactobacillus or Bifidobacteria.
 23. A coated component made inaccordance with the method of claim
 1. 24. A method of delivering acomponent to the colon of an animal comprising: coating the componentwith one or more prebiotics; and orally administering the coatedcomponent to the animal.
 25. The method of claim 24 wherein theprebiotic is a fructose-based oligosaccharide, peptide, protein, orlipid that is not digested or absorbed in a stomach or small intestine,but is fermented by bacteria present in the colon.
 26. The method ofclaim 24 comprising coating the component with a mixture of two or moreprebiotics.
 27. The method of claim 26 wherein one of the prebiotics isfructo-oligosaccharide.
 28. The method of claim 24 comprising coatingthe component with a mixture of one or more prebiotic and one or moreflavoring agent.
 29. The method of claim 24 wherein the component is oneor more of a mineral, vitamin, drug, bacteria, yeast, immune stimulator,nutrient, nutraceutical, electrolyte, chelated mineral, mold, enzyme,energy-providing compound, antibody, or acid.
 30. A composition forcolon-targeted delivery comprising: one or more components to bedelivered to the colon; and a fructose-based non-digestible carbohydratecoating surrounding the component.
 31. The composition of claim 30wherein the fructose-based non-digestible carbohydrate isfructo-oligosaccharide.
 32. The composition of claim 30 wherein thefructose-based non-digestible carbohydrate is inulin.
 33. Thecomposition of claim 30 wherein the fructose-based non-digestiblecarbohydrate is neosugar.
 34. The composition of claim 30 wherein thecoating further comprises a flavor enhancing agent.
 35. The compositionof claim 30 wherein the component is one or more of a mineral, vitamin,drug, bacteria, yeast, immune stimulator, nutrient, nutraceutical,electrolyte, chelated mineral, mold, enzyme, energy-providing compound,antibody, or acid.
 36. The composition of claim 35 wherein the componentis one or more beneficial bacteria from the genus Lactobacillus orBifidobacteria.
 37. A composition for colon-targeted deliverycomprising: one or more components to be delivered to the colon; and acoating of one or more prebiotics surrounding the component, wherein atleast one of the prebiotics is a fructose-based non-digestiblecarbohydrate.
 38. A method of masking the flavor of a component to beadministered orally to an animal comprising coating the component withcombination of a fructose-based non-digestible carbohydrate and aflavoring agent.
 39. The method of claim 38 wherein the fructose-basednon-digestible carbohydrate is fructo-oligosaccharide, inulin, orneosugar.
 40. A method of enhancing the flowability of a componentcomprising coating the component with a fructose-based non-digestiblecarbohydrate.
 41. The method of claim 40 wherein the fructose-basednon-digestible carbohydrate is fructo-oligosaccharide, inulin, orneosugar.